Bladder cancer is the fourth most common cancer among men and the ninth most common cancer among women. It is estimated that each year in the United States, more than 60,000 people develop bladder cancer, of whom more than 13,000 ultimately die of this disease. Bladder cancer most commonly occur in individuals over 60 years of age. Cigarette smoking, exposure to certain industrially used chemicals such as arylamine derivatives, and diet high in fried meat and fat are strongly associated with the development of bladder cancer.
The urinary bladder is made up of four layers: epithelium, lamina propria, muscularis propria or detrusor muscle, and perivesical soft tissue. The epithelium, also referred as transitional urothelium or epithelium, lines the bladder and is in contact with the urine. Transitional urothelial carcinomas are the most common type of bladder cancer, accounting for more than 90% of all bladder cancer. Clinically, transitional urothelial carcinomas are separated into superficial tumors and muscle invasive tumors. Superficial tumors are those that either do not invade, or those that invade but stay superficial to the deep muscle wall of the bladder. Muscle invasive tumors invade the detrusor muscle (pathologic stages pT2-pT4) and are highly aggressive. When bladder cancer invades the muscular layers of the bladder wall it may spread by way of the lymph and blood systems to invade bone, liver, and lungs.
The treatment of muscle invasive tumors requires cystectomy, a surgical procedure that removes all or part of the urinary bladder. Superficial bladder cancer can be treated without cystectomy, usually by transurethral resection (TUR) with or without adjuvant intravesical chemotherapy or immunotherapy. Superficial bladder cancer include noninvasive papillary carcinoma, superficial invasive carcinoma, and carcinoma in situ (CIS). Carcinoma in situ of the urinary bladder is a highly malignant and aggressive cancerous lesion.
Patients with carcinoma in situ of the urinary bladder are usually treated with transurethral resection or fulguration followed by adjuvant intravesical chemotherapy or immunotherapy. Adjuvant chemotherapy or immunotherapy followed by transurethral resection may reduce the rate of recurrence of bladder cancer and increase the overall survival rate. Currently, Bacille Calmette-Guerin (BCG) is the commonly used immunotherapeutic agent, and Mitomycin C the chemotherapeutic agent in conjunction with transurethral resection. It has been shown however that the efficacy of BCG and Mitomycin C is limited and some patients are refractory to BCG or Mitomycin C intravesical treatment.
VALSTAR® (Indevus Pharmaceuticals, Inc., Lexington, Mass.) is currently the only drug approved by the U.S. Food and Drug Administration (FDA) for therapy of BCG-refractory carcinoma in situ of bladder cancer, and has been used for treating patients who are not candidates for cystectomy. VALSTAR® is a sterile solution for intravesical instillation of valrubicin, which is a chemotherapeutic anthracycline derivative.
Clinical studies showed that many patients who received intravesical VALSTAR® treatment experienced local adverse events during or shortly after instillation of VALSTAR®, and within 1 to 7 days after the instillate is removed from the bladder. In a study among 170 patients who received 800 mg dose of VALSTAR® in a multiple-cycle treatment regimen, approximately 28 percent of the patients experienced bladder spasm and 22 percent experienced bladder pain. Bladder spasm is undesirable since it leads to leakage of the medicine and reduce the efficacy of the treatment. Therefore, further developments are needed in the treatment of bladder cancer, especially superficial bladder cancer.